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[Comment] Daratumumab in multiple myeloma

It is easy to be overwhelmed by hype in cancer research, with promising new discoveries often portrayed as so-called game changers.1 Most new treatments for cancer are far from being transformative, but daratumumab is possibly a rare exception. It targets CD38, an antigen that is uniformly expressed in myeloma cells.2 As the most anticipated new drug in multiple myeloma in more than a decade, daratumumab has all the features that are necessary to make a substantive difference in a devastating cancer, which—despite many advances—manages to outwit all available treatments over time: a novel mechanism of action, single-agent activity, non-cross resistance, and safety.

BEACH washed up

Attempts to gauge the effect of big changes to chronic disease management and primary care being planned by the Federal Government have been dealt a blow by revelations one of the most extensive and sustained studies of general practice in the world is facing shutdown.

The long-running Bettering the Evaluation and Care of Health (BEACH) program, which began tracking the activities of Australian GPs in 1998, is being wound up after the Federal Department of Health announced it would not be renewing funding for the research after the current contract expires on 30 June.

The program’s director, Professor Helena Britt of Sydney University’s Family Medicine Research Centre, said the Department’s decision had come at a time when the program was already facing a funding crunch caused by a downturn in contributions from other sources including non-government organisations and pharmaceutical companies.

“BEACH has always struggled to gain sufficient funds each year,” Professor Britt said. “However, this notification comes when we also have a large shortfall in funding coming from other organisations…due to the closure of many government instrumentalities and authorities, and the heavy squeeze on pharmaceutical companies’ profits resulting from changes to the PBS.

“We therefore have no choice but to close the BEACH program.”

The announcement has been met with shock and dismay by medical practitioners and researchers. Professor Britt said she had been inundated with inquiries and messages of support from individuals and groups around the country and internationally.

BEACH’s shutdown comes at a particularly uncertain time for general practice as the Government moves to implement its Health Care Homes model of chronic care while simultaneously trialling its My Health Record e-health record and persisting with a four-year freeze on Medicare rebates.

Professor Britt said the BEACH data, which is drawn from an annual sample of GPs providing detailed information on everything from the hours they work to the diseases and other conditions they treat, was a unique resource, and the program’s closure would “leave Australia with no valid reliable and independent source of data about activities in general practice”.

“BEACH has been the only continuous national study of general practice in the world which relies on random samples of GPs, links management actions to the exact problem being managed, and provides extensive measurement of prevalence of diseases, multi-morbidity and adverse medication events,” a statement issued by the Family Medicine Research Centre said.

The data from the latest BEACH survey, which began in April last year and closed at the end of March this year, is being collated and Professor Britt said she hoped to issue a report on the results, possibly in mid-June.

Asked about the possibility of funding coming from other sources, Professor Britt said it was “early days”.

One of the biggest concerns is what will happen to the rich store of data accumulated through the program’s 18 years of operation, during which time more than 11,000 GPs have been surveyed.

Professor Britt said the data was used by a huge range of researchers and organisations, and her group was looking at ways to ensure people would continue to have access to it.

“We would be happy to find a place with a senior analyst who could take request to analyse the data for specific purposes,” she said. “We would like to be able to keep that access up there for at least a little while.”

Adrian Rollins

[Correspondence] PATHWAY-2: spironolactone for resistant hypertension – Authors’ reply

We thank Boutari and colleagues, Gkaliagkousi and colleagues, and Dale and colleagues for their interest in our findings in the PATHWAY-2 study.1 As noted at the end of our Research in context, we also believe that there might be substantial overlap between primary aldosteronism and resistant hypertension. Plasma aldosterone, measured in our substudy was not predictive on its own of blood pressure response (unpublished). However, PATHWAY-2 shows that in patients receiving treatment with three drugs (angiotensin-converting-enzyme inhibitor or an angiotensin II receptor blocker, plus a calcium channel blocker, plus a thiazide-like diuretic—ie, A + C + D) at baseline, plasma renin values in the lower third of the normal range are inappropriately low and might be the sole clue to underlying primary aldosteronism.

[Correspondence] A step forward for data protection and biomedical research

To update previous correspondence to this journal,1 we are pleased to report that, in large part through the efforts of the biomedical research community, a European General Data Protection Regulation that is favourable for research was agreed by Member States and Parliament in December, 2015.2 Although the Regulation will probably not apply until mid-2018, now is an appropriate time to highlight the implications for biomedical research.

The world is turning to flab

Rich countries are facing an epidemic of severe obesity and around one in five worldwide will be obese by the middle of next decade unless there is a major slowdown in the rate at which people are putting on weight, according to a major international study involving data from 19 million adults across 186 countries.

Already, more than 2 per cent of men and 5 per cent of women are severely obese, and researchers have warned that the prevalence is set to increase and current treatments like statins and anti-hypertensive drugs will not be able to fully address the resulting health hazards, leaving bariatric surgery as the last line of defence.

In a result which underlines the extent of the obesity challenge, research by the NCD Risk Factor Collaboration* has found that that between 1975 and 2014, the prevalence of obesity among men more than trebled from 3.2 per cent to 10.8 per cent, while among women it surged from 6.4 to 14.9 per cent.

The study’s authors warned that on current trends, 18 per cent of men and 21 per cent of women will be obese by 2025, meaning there was “virtually zero” chance of reaching the global target of halting the prevalence of obesity at its 2010 level.

Instead, in the next nine years severe obesity will supplant underweight as a bigger public health problem, especially for women.

“The world has transitioned from an era when underweight prevalence was more than double that of obesity, to one in which more people are obese than underweight,” the study, published in The Lancet, said.

But although the world is getting fatter, it is also getting healthier, confounding concerns about the detrimental health effects of being overweight.

Writing in the same edition of The Lancet , British epidemiologist Professor George Davey Smith said that the increased in global body mass index (BMI) identified in the study had coincided with a remorseless rise in average life expectancy from 59 to 71 years.

Professor Davey Smith said this was a paradox, given the “common sense view that large increases in obesity should translate into adverse trends in health”.

Generally, a BMI greater than 25 kilograms per square metre is considered to be overweight, while that above 30 is obese and above 35, severely obese.

As the BMI increases above the “healthy” range, it is associated with a number of health consequences including increased blood pressure, higher blood cholesterol and diabetes.

The fact that increased BMI has not so far been associated with decrease longevity has led Professor Davey Smith to speculate that in wealthier countries access to cholesterol lowering drugs and other medications have dampened the adverse health effects, sustaining improvements in life expectancy despite increasing weight.

But he warned this effect would only be limited – many people would not be able to afford such treatments, and pharmacological interventions can only alleviate some of the health problems associated with being obese, meaning many health effects are likely to emerge in greater number later on as the incidence of obesity increases.

One of the most important aspects of the NCD Risk Factor Collaboration report is the insight it provides into differences in the nature and prevalence of weight problems between countries and regions.

For instance, it shows that the biggest increase in men’s BMI has occurred in high-income English-speaking countries, while for women the largest gain has been in central Latin America.

At the extreme, the greatest prevalence of overweight and obesity was in American Samoa, where the age standardised mean BMI for was 32.2, and for women, 34.8. Other areas where the mean BMI for both men and women exceeded 30 included Polynesia, Micronesia, the Caribbean, and several countries in the Middle East and north Africa, including Kuwait and Egypt.

The researchers found that male and female BMIs were correlated across countries, though women on average had a higher BMI than men in 141 countries.

But, in a sign that the rate of weight gain in a country may slow after a certain point, the researchers found that from 2000 BMI increased more slowly than the preceding 25 years in Oceania and most high income countries.

Alternatively, it sped up in countries where it had been lower. After 2000, the rate of BMI increase steepened in central and eastern Europe, east and southeast Asia, and most countries in Latin America and Caribbean.

The results suggest that public health campaigns and other polices aimed at curbing weight gain and encouraging healthier diets and more physical exercise are so far having little effect, spurring policymakers to consider different measures.

Though not canvassed in the study, one idea gaining support intnationally is for governments to impose a tax on sugary foods.

The United Kingdom will levy a tax on sugary drinks from next year, similar to one already in place in Mexico, and the World Health Organisdaiton has backed the policy as a way to curb the rapid increase in cases of diabetes in the world.

While overweight and obesity has become a major public health problem, particularly in wealthier countries, inadequate nourishment remains a health scourge in much of the world.

The NCD Risk Factor Collaboration report shows that millions continue to suffer serious health problems from being underweight, and warned that “the global focus on the obesity epidemic has largely overshadowed the persistence of underweight in some countries”.

As in other respects, global inequality in terms of weight have increased in the past 40 years, and while much of the world is getting fatter, in many areas under-nutrition remains prevalent.

The study found that more than 20 per cent of men in India, Bangladesh, Timor Leste, Afghanistan, Eritrea, and Ethiopia are underweight, as are a quarter or more of women in Bangladesh and India.

* The study drew on 1698 population-based data sources involving body mass index measurements taken from 9.9 million men and 9.3 million women in 186 countries between 1975 and 2014.

Adrian Rollins

 

[Comment] Expression of concern—Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study

On Nov 24, 2011, The Lancet published a research article on tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite.1 3 years later, several of the authors, together with others, raised concerns about the validity of this work. The Karolinska Institute launched an investigation led by Professor Bengt Gerdin into papers on the development of the technique. Gerdin’s report was followed by a second evaluation that largely cleared concerns regarding The Lancet paper. More recently, a documentary series on Swedish television again cast doubt on this work and precipitated public uncertainty about the research from Karolinska.

Shingles vaccine to cost unless you are 70

A vaccine to prevent the painful and potential deadly shingles infection will be available to 70-year-olds free of charge from November this year.

But those in their 50s, 60s, and 80s will continue to have to fork out $200 or more for a dose of the Zostavax vaccine if they want to be protected from the viral infection.

The Federal Government has allocated $100 million over four years to provide the vaccine free through the National Immunisation Program (NIP), and expects around 240,000 people to be immunised each year.

It is also funding as five-year catch up program during which Australians aged between 71 and 79 years are eligible to receive Zostavax through the NIP. Altogether, the Government expects around 1.4 million will be administered the vaccine through this initiative.

But other vulnerable groups, particularly those in their 60s, will have to make their own arrangements if they want to be protected from the infection, the risk and severity of which increases markedly with age.

Shingles is caused by the reactivation of the varicella-zoster virus that causes chicken pox in children. Following initial infection, the virus lies dormant in nerve roots near the spinal cord, and can reactivate at any time.

The infection often appears as a painful rash or blisters on the skin, and the associated pain can be excruciating.

In addition to the rash, in 50 per cent of cases shingles can lead to post-herpetic neuralgia, a chronic and debilitating form of neuropathic pain that can persist months or even years after the rash has healed.

Drug company bioCSL said that more than 97 per cent of Australians had developed antibodies to the varicella-zoster virus by the time they were 30 years of age, indicating almost universal potential to develop shingles among the adult population – though medical experts warn there is no way to predict who might develop shingles, or when.

Zostavax is approved for the prevention of shingles in those aged 50 years or older, and for the over 60s is also indicated as a protection against post-herpetic neuralgia and as a treatment to reduce acute and chronic zoster-associated pain.

But even though shingles is recognised as a risk for those 50 years and older, the medicines watchdog has resisted calls for Zostavax to be subsidised for those aged 50 to 69 years because of the vaccine’s limited longevity and doubts about the cost effectiveness of the measure.

Research indicates the vaccine is only effective for around 10 to 12 years, meaning that a typical 50-year-old receiving it would need at least two, and possibly three or more boosters to maintain protection.

Even though prevalence increases with age, from around 2 infection per 1000-person years in the under 50s to 5 per 100 person-years among those in their 50s, to 7 per 1000 among those in their 60s, and 10 per 1000 in 70-year-olds, an evaluation by the US Centers for Disease Control and Prevention found that Zostavax was not cost effective for those in their 50s.

It calculated that for every 1000 people receiving the vaccine at age 50, only 25 shingles cases and one case of shingles-related pain would be prevented.

Australia’s Therapeutic Goods Administration has done significant work evaluating the veracity of drug company claims about the longevity and effectiveness of the vaccine, and in 2014 advised against subsidising Zostavax for 60-year-olds because of “unacceptable assumptions” in the economic case for the proposal.

Adrian Rollins

A real knees up

Patients suffering osteoarthritis and other debilitating knee complaints have reported major improvements in pain and mobility following injections with their own stem cells.

In a development that could transform the lives of thousands and reduce the need for costly joint replacement surgery, scientists at the Melbourne Stem Cell Centre have reported “excellent” results in a trial of the use of stem cells to manage osteoarthritis and isolated cartilage lesions.

Interim results of the trial show there was a statistically significant improvement in pain and function after one month, and after nine months more than 65 per cent of patients aged 41 to 60 years experienced at least a 50 per cent reduction in pain.

The researchers, led by the Centre’s Chief Clinical Investigator, Dr Julien Freitag, were particularly excited by the progress of a 26-year-old patient with osteo chondritis dessicans.

The patient, who had undergone seven major knee operations in 12 years, joined the trial in June last year and MRI scans since then show that his cartilage has begun to regrow and pre-existing damage to the knee is starting to reverse.

While the privately-funded trial is yet to be completed, Dr Freitag said the interim results were “extremely encouraging”, and confirmed that the promise of regenerative therapies such as the use of stem cells was now “closer to reality”.

He said MRI analysis showed consistent stabilisation and a halt to the progress of arthritis in test subjects, and regrowth of cartilage in some.

Importantly, the improvements have been sustained beyond 12 months.

The technique involves using liposuction to obtain a sample of the patient’s stem cells, which are isolated and expanded before being injected back into them.

The results have been so promising that patients in the trial’s control group have been invited to undergo the treatment after 12 months of data collection.

See also: Push for crack on unproven stem cell therapies

Adrian Rollins

Military should get annual check up

Australian Defence Force personnel would undergo annual mental health checks under plans backed by the AMA to tackle rates of depression, post-traumatic stress disorder and suicidal thoughts in the military.

A parliamentary committee inquiring into the mental health of soldiers, sailors and air force personnel found that although in the short term they were no more prone to mental health problems than the broader community, the nature of their work meant the types of problems they experience are not the same.

The 2010 ADF Mental Health Prevalence and Wellbeing Study found that 22 per cent of Defence personnel experienced a mental disorder in the previous 12 months, roughly similar to that found in a sample of general members of the community, while almost 7 per cent who suffered multiple problems.

But although, in the short term, the prevalence of problems was approximately the same, over their lifetime, ADF personnel were found to be more at risk of mental health problems.

Military personnel were found to be less prone to alcohol abuse, but they were more likely to suffer depression, and to think about and plan suicide. The most common mental health problem, however, was anxiety, particularly post-traumatic stress disorder.

AMA President Professor Brian Owler said this reflected the particular characteristics of their work, including experiences during deployment overseas and long absences from family and support networks.

Professor Owler said a recommendation from the Foreign Affairs, Defence and Trade References Committee for annual mental health screening was a welcome proposal.

“Annual screening would help ensure that mental health problems are identified at a much earlier stage, would support early intervention, and lead to much better mental health outcomes for affected personnel,” the AMA President said.

He also endorsed the Committee’s call for a unique identifier number for veterans linked to their service and medical records.

In 2013, the Federal Government gave in-principle support to a similar idea put forward by the Joint Standing Committee on Foreign Affairs, Defence and Trade, but Professor Owler said there appeared to have been little progress made on it since.

“A unique or universal identifier could help improve health outcomes for these patients,” Professor Owler said.

The AMA President said it would support the transition of personnel out of Defence Force-funded health services into those provided by the Department of Veterans’ Affairs or the mainstream health system, and would enable tracking of the health of former ADF personnel over time, which was critical to research.

He said there was strong support for the idea among veterans’ groups, and called on the Government and bureaucracy to fast-track the initiative.

Adrian Rollins

 

Two energy drinks a day may send a doctor your way

Many Australians turn to energy drinks to reduce fatigue, increase wakefulness, and improve concentration and performance, but a study has found that drinking more than two energy drinks a day can cause adverse heart reactions, including a fast heartbeat, heart palpitations, and chest pain.

Researchers from the University of Adelaide surveyed patients aged 13 to 40 years who attended an emergency department in South Australia with heart palpitations, and found 70 per cent had consumed some version of an energy drink.

Dr Scott Willoughby, co-author of the study, said that the study was able to find a direct link between energy drink consumption and hospital admissions for adverse heart reactions.

“Of the patients surveyed, 36 per cent had consumed at least one energy drink in the 24 hours prior to presenting at the hospital, and 70 per cent had consumed some sort of energy drink in their lifetime,” Dr Willoughby said.

“Those patients who were heavy consumers of energy drinks were found to have significantly higher frequency of heart palpitations than those who consumed less than one a day.

“And importantly, fast heartbeat, heart palpitations, and chest pain was seen in energy drink consumers who were healthy and had no risk factors for heart disease.”

AMA Vice President, Dr Stephen Parnis, told the Herald Sun that people did not realise the serious health repercussions of energy drinks, some of which have the same amount of caffeine as 10 or 20 cups of coffee.

“Poisoning is not too strong a word to use for the effects of these drinks on some people,” Dr Parnis said.

“I have seen teenagers present in emergency with heart rates of 200 beats per minute or who are so stimulated that their behaviour is extremely distressing to their parents and the people around them.

“At the bare minimum, energy drinks should come with warning labels.

“I think that preventing sales of these drinks to people under 18 is something that we need to look at very closely.”

The study was published in International Journal of Cardiology.

Kirsty Waterford